A tudor domain protein SPINDLIN1 interacts with the mRNA-binding protein SERBP1 and is involved in mouse oocyte meiotic resumption

Mammalian oocytes are arrested at prophase I of meiosis, and resume meiosis prior to ovulation. Coordination of meiotic arrest and resumption is partly dependent on the post-transcriptional regulation of maternal transcripts. Here, we report that, SPINDLIN1 (SPIN1), a maternal protein containing Tudor-like domains, interacts with a known mRNA-binding protein SERBP1, and is involved in regulating maternal transcripts to control meiotic resumption. Mouse oocytes deficient for Spin1 undergo normal folliculogenesis, but are defective in resuming meiosis. SPIN1, via its Tudor-like domain, forms a ribonucleoprotein complex with SERBP1, and regulating mRNA stability and/or translation. The mRNA for the cAMP-degrading enzyme, PDE3A, is reduced in Spin1 mutant oocytes, possibly contributing to meiotic arrest. Our study demonstrates that Spin1 regulates maternal transcripts post-transcriptionally and is involved in meiotic resumption.Ting Gang Chew, Anne Peaston, Ai Khim Lim, Chanchao Lorthongpanich, Barbara B. Knowles, Davor Solte

The delayed and cumulative consequences of traumatic stress: Challenges and issues in compensation settings

Delayed onset posttraumatic stress disorder has been a challenging issue in medico-legal settings. Prospective studies have done much to characterise the validity of this construct and the prevalence in various populations. The delayed impact of these events places significant challenges on a plaintiff in establishing a causal link to some distal exposure. Furthermore, the literature highlights that depression is a frequent independent outcome from posttraumatic events, independent of the frequent comorbidity for posttraumatic stress disorder. To date, there has been little examination of the commonality of the underlying mechanisms of aetiology between depression and posttraumatic stress disorder. The concepts of sensitisation and kindling have been extensively discussed as underlying mechanisms relevant to a range of psychiatric disorders. This idea of increasing sensitisation of individuals who have multiple traumatic stress exposures is of critical importance to understanding the shared aetiology of major depressive disorder and posttraumatic stress disorder. Furthermore, the neural circuitry involved in these conditions particularly involves the amygdala, medial prefrontal cortex and anterior cingulate. Given the shared aetiological mechanisms, it is probable that the delays in treatment which have been demonstrated to be important factors for decreasing the probability of a full treatment response in depression are equally relevant to posttraumatic stress disorder. This raises important issues about the liability of employers particularly in the emergency services for vetting individuals where there is a foreseeable risk. A further challenge in litigation settings is the increasing body of evidence linking posttraumatic stress disorder and depression to cardiovascular disease and hypertension.Alexander C. McFarlan